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Updated: Mar 13, 2026
Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells
Published on: March 31, 2021
Cajal-Retzius fate specification is disrupted by constitutive activation of β-Catenin in hem progenitors
Amrita Singh1, Arpan Parichha1,2,3, Debarpita Datta1
1Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
Insights
Constitutively stabilizing beta-Catenin in mouse cortical hem progenitors produced neurons but not Cajal-Retzius (CR) cells. A Tbr2+ differentiation stage appears crucial for CR cell identity acquisition.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Cajal-Retzius (CR) cells are the first cortical neurons, crucial for brain development.
- The cortical hem, a signaling center, is a primary source of CR cells.
- Hem progenitors experience high WNT signaling, influencing CR cell production.
Purpose of the Study:
- To investigate if stabilizing beta-Catenin (gain of function) in hem progenitors affects CR cell production.
- To understand the role of WNT signaling pathway in CR cell differentiation.
Main Methods:
- Utilized a mouse model with constitutive beta-Catenin stabilization in cortical hem progenitors.
- Employed single-cell transcriptomics to analyze neuronal differentiation trajectories.
- Examined molecular markers of CR cell identity.
Main Results:
- Neurons were generated from hem progenitors with stabilized beta-Catenin.
- These neurons failed to acquire molecular CR cell identity.
- A Tbr2+ immature CR cell stage, normally present, was absent in beta-Catenin gain-of-function models.
Conclusions:
- Cortical hem progenitors are sensitive to beta-Catenin levels.
- A Tbr2+ stage is critical for Cajal-Retzius cell identity.
- Aberrant WNT signaling disrupts CR cell development.
Abstract:
Cajal-Retzius (CR) cells are the earliest born neurons in the cerebral cortex, and they have been implicated in regulating neuronal migration and development of circuitry. A major source of CR cells is the cortical hem, a signaling center at the dorsal telencephalic midline. The hem functions as the hippocampal organizer via canonical WNT signaling and hem progenitors are therefore exposed to high levels of WNT ligands. We tested whether constitutive stabilization of β-Catenin (Ctnnb1 gain of function, GOF) in the mouse cortical hem progenitors supports CR cell production. We find that, although neurons are produced from the hem, they do not acquire molecular features of CR cell identity. The trajectory of differentiation examined using single-cell transcriptomics reveals that immature CR cells normally display a Tbr2+ stage, which is absent upon Ctnnb1 GOF. These data indicate that CR progenitors in the hem are sensitive to levels of stabilized β-Catenin and that a Tbr2+ stage may be important for the acquisition of CR cell identity.
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